Applications of Particle Accelerators in Medical Physics G Cuttone Istituto

Document Sample
Applications of Particle Accelerators in Medical Physics G Cuttone Istituto Powered By Docstoc
					Applications of Particle Accelerators in Medical Physics.


                               G. Cuttone,
  Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud
           V. S. Sofia, 44 Catania Italy- Cuttone@lns.infn.it



  1. INTRODUCTION

      Particle accelerators are often associated to high energy or nuclear physics. As well
  pointed out in literature [1] if we kindly analyse the number of installation worldwide we can
  easily note that about 50% is mainly devoted to medical applications (radiotherapy, medical
  radioisotopes production, biomedical research). Particle accelerators are also playing an
  important indirect role considering the improvement of the technical features of medical
  diagnostic. In fact the use of radionuclide for advanced medical imaging is strongly
  increasing either in conventional radiography (CT and MRI) and also in nuclear medicine for
  Spect an PET imaging. In this paper role of particle accelerators for medical applications will
  be presented together with the main solutions applied.
   2. THE ROLE OF PARTICLE ACCELERATORS COMBATING CANCER.

     At the beginning of the third millennium one European citizen out of three will have
to deal with a cancer episode in the course of his/her life. Worldwide the estimated
number of new cancer cases each year is expected to rise from 10 millions in 2000 to 15
millions by 2020. Cancer is currently the cause of 12% of all deaths worldwide. Within
the European union it is over 1,5 million new cancer cases that are diagnosed every year
and over 920000 people die of cancer with the two leading cause of cancers in Europe are
Breast and Prostate. Therefore combating cancer is a major societal and economical
issue for Europe and to face up these new challenges strong mobilisation among the
scientific community and industrial manufacturers is needed.
     Today’s approaches to treat cancer are the surgical removal of the tumour tissue,
radiotherapy, chemotherapy, and immunotherapy. Most scientists are confident that in the
long run significant improvements in cancer cure will come from immunotherapy and/or
gene therapy and drug targeting ; research towards such systemic treatments is and will
be of the utmost importance. However, in the mean time, radiotherapy either combined
with surgery or as main treatment modality still remains the most effective technique to
treat cancer.
     More than a half of all cancer patients are now treated by radiation therapy thanks to
the technical progress made with irradiation equipment in the last ten years. For external
radiation therapy (RT), for instance, high energy photon or electron beams are mainly
produced by linear accelerators, while a very limited number of proton synchrotrons or
cyclotrons are used for the treatment of cancers close to vulnerable organs such as the
eyes and the optical and auditory nerves, spinal cords. For internal radiation therapy,
brachytherapy, radioactive sources are put in the tumour with undeniable advantages for
the patient in given situations.
     In an abstract from Annex A of "Europe Against Cancer" [2] in 1994, the present
status of cured patients following a specific treatment shows that in Europe at present
45% of all the treated patients are "cured", which means that these patients have a
symptom-free survival period exceeding five years. About 90% of the cured patients (i.e.
40% of the total) are cured because of loco-regional control of the primary tumour, i.e.
because of surgery and radiotherapy. Of course, the treatments are almost always
accompanied by chemotherapy to prevent the spreading of metastasis. In fact surgery and
radiotherapy alone are successful in 22% and 12% of the cases respectively. When
combined, they account for another 6% of the cases so that radiotherapy is involved in
almost half of the curative treatments of loco-regional type. Despite a widespread belief,
all the other systemic treatments account for 5% only of the cured patients. There is
ample space for improvements here, because 37 % of the tumours are metastatised at the
moment of diagnosis and cannot be cured with loco-regional treatments alone.

    Three strategic approaches are generally proposed:

       •   Early detection and improved diagnosis based on widespread screening with
           the aim of reducing the number of late diagnoses.
       •   Improved local treatment, avoiding poor treatments, to treat tumours with
           difficult localisations and tumours which are radio-resistant to conventional
           radiotherapy.
       •   Improved systemic treatments combined with local treatments which are able
           to reduce the tumour mass significantly.

    Improving loco-regional treatments is essential for at least two reasons. First, 18% of
all the patients die because of a primary tumour without metastases. This implies that the
percentage of the cured patients could pass from 45% to about 65 %, if all primary
tumours could be locally controlled. Secondly, in the long term “immunochemotherapy
might be extremely useful in cancer treatment; it will, however, only be effective against
a relatively small number of cells and such treatments will thus need to be used in
conjunction with other anti-cancer modalities such as surgery, radiotherapy and
chemotherapy".
    For all these reasons it is generally approved that to increase the dose at the target or to
get a better dose conformation to spare surrounding health tissue it is mandatory to
implement new techniques like Conformal Radiotherapy, Intensity Modulation
Radiotherapy (IMRT) or hadrontherapy (HT). These techniques together with stereotactic
treatment (ST) or brachytherapy (BT) represent nowadays the new frontier of the
radiotherapy daily implemented in the clinical reality of European Union (EU) countries.
    The development of three-dimensional (3D) conformal radiotherapy, in which the
high-dose volume matches the target volume and avoids radiosensitive normal tissues,
has been a major theme for improving the physical basis of radiotherapy [3]. Intensity-
modulated radiation therapy (IMRT) is the most advanced form of conformal
radiotherapy. It is anticipated [4] that in the next ten years it will be routinely possible to
automatically shape radiation fields, modulate the intensity such modulation under
computer control, verify that radiotherapy is accurately delivered, predict the clinical
outcome via biological models, and if not eliminate uncertainties, quantify them. It may
become possible to customize radiotherapy to radio sensitivities of individual patients.
    Conformal radiotherapy may be broadly divided into two classes of techniques, i.e.
those which employ field-shaping alone and those which also modulate the intensity of
fluence across the geometrically-shaped field. The basic idea behind IMRT is that by
sparing more volume of the organs at risk the dose to the planning treatment volume can
be escalated and thus result in improved tumour control probability. The types of
radiation used in IMRT may be photons, protons and light ions.

   Protontherapy (PT) and heavier charged beam therapy (IT) shares with photon IMRT
the characteristics of an enhanced precision in the dose delivery to the target. For these
reason protontherapy scores, as photon IMRT, better clinical results than conventional
radiotherapy but also faces the same challenges of achieving a higher precision in target
localisation. Moreover also from the radiobiological point of view protons and especially
heavy ions have demonstrated major effects giving possibility to change the fractioning
scheme (ipofractioning) and the total dose.

  An other challenge concerns brachytherapy where high quality treatment requires
development of new radiation delivery systems and sensors for checking the main
biological and dosimetric parameters of the patient. Short life radioactive substances are
incorporated in the cancerous tumour allowing the patient to spend a quasi normal life
with minor limitations. Brachytherapy, also known as Curie therapy is undergoing rapid
changes in technology. In Europe, high dose rate (HDR) brachytherapy using after-
loaders with Iridium sources is the most common technology. But, specially for the
treatment of prostate cancer, low dose rate (LDR) brachytherapy using sealed seeds filled
with local action radioisotope such as Iodine 125 or Palladium 103 are increasingly used.
Innovative research have to be carried out in order to ensure a better quality and
efficiency of treatments. This advanced brachytherapy (BT) treatment needs validation
and new requirements for patient safety. On the other hand accelerator based facilty have
to be developed in order to get reliable production of those radionuclides.
   Although IMRT, external beam radiotherapy (photons, protons, hadrons) and
advanced brachytherapy (BT) promise great benefits for optimised cancer treatment, a
considerable number of technical restrictions and basic questions have to be resolved to
realise the expected benefits.
   In radiation oncology (IMRT, PT and BT), the main difficulty is to deliver both a
precise and accurate large dose of radiation to destroy cancer cells in a diseased organ
and a dose as low as possible to sound organs. Delivered doses to tumours being highly
above the lethal level for a total body irradiation, thus doses have to be delivered with
extreme precaution. In coming years, it will be necessary to find treatment protocols
based on IMRT and advanced BT techniques. It is therefore crucial to be able to more
accurately locate the tumour in treatment, to accurately determine the dose required and
to fully spare organs that are vulnerable or present a high structural heterogeneity, in
order to reduce the doses delivered to healthy organs with proper monitoring throughout
the duration of the treatment.
   Functional imaging by means of positron emission tomography (PET) or single photon
emission computerized tomography (SPECT) can facilitate the evaluation of tumour
physiology, metabolism and proliferation [5]. These are parameters determining outcome
to radiotherapy treatment. PET can be used to get also quantitative information about the
the in vivo distribution of positron-emitting radioisotopes (Fluorine-18, Carbon-11,
Oxygen-15) that can be added or substituted into biological relevant compounds. SPECT
may be used to image compounds labelled with indium-111, technetium-99m, and
Iodine-123 in vivo. The application of these techniques represents a new frontier in
combating cancer permitting not only the early diagnosis of tumour but also the
biological target definition in radiotherapy like tumour metabolism, hypoxia, growth
factor receptor expression, tumour apoptosis. These parameters can be used as predictors
or early markers of response to radiotherapy, opening a new frontier of study and clinical
application.

  3. ACCELERATORS FOR MEDICAL APPLICATIONS: A SHORT HISTORY

  The development of particle accelerators started in the past century and was well
summarized by P.J Bryant [6]. It is mainly based on three acceleration mechanism:
  DC Acceleration
  Resonant Acceleration
  Betatron Mechanism
   Following the first mechanism a wide set of electrostatic machines (Cockroft Walton
generator, Van Der Graaf generator single or double stage) have been developed. Their
use for medical applications has been very limited.
   Resonant acceleration proposed by Ising in 1924 is based on the use of alternating
electric fields. He suggested to accelerate particles with a linear series of conducting drift
tubes and in 1928 Wideroe demonstrates his validity building a 1 MhZ, 25 kV oscillator
able to accelerate 50 keV potassium ions. He realized the first linear accelerator (LINAC)
prototype. At that time the realization of a LINAC was really difficult so that we have to
wait until 1930 for the realization of the first real particle accelerator based on this
mechanism. In fact at that time Lawrence realized the first fixed frequency cyclotron
accelerating 1.25 MeV proton beam. Cyclotron was limited in energy by relativistic
effects so that we had to wait for increasing energy until 1944. At that time Veksler
discovered the principle of phase stability and invented the synchrotron. LINAC,
CYCLOTRON and SYNCHROTRON nowadays are particle accelerators used for
medical applications.
   Betatron mechanism originally discovered by Wideroe in 1923 and never published,
found his proof in 1940 when Kerst re-invents the betatron and built the first working
machine for 2.2 MeV electrons. Betatrons were used in radiotherapy for many years.
Today they have been fully replaced by electron LINAC.

   4. ACCELERATORS FOR RADIOTHERAPY

   In conventional radiotherapy, electron LINAC are mainly used. A 3 GHz accelerating
structure is used. The electrons are thermo-ionically emitted from a concave metal
cathode at 1000 °C and accelerated in the gun to about ¼ the velocity of light by a pulsed
DC electric field. Then they are formed into a pencil beam by a convergent electric filed
between the gun electrodes. The RF electric field in the accelerating tube then forms the
electron into bunches and accelerates them to more than 99% of light velocity, increasing
their mass. The electrons are then used to bombard a target tipically done in tungsten.
Electrons hitting the target will produce Bremstralung Radiation in the forward direction.
X-rays so emitted are used for the therapy. Two sets of tungsten blocks allow the sizes of
the radiation beam (square or rectangular sections) to be adjusted. All modern medical
electron linacs employ an isocentric gantry. The accelerator wave guide is mounted in the
gantry, either parallel to the gantry axis if a beam bending magnet is employed or
perpendicular to the gantry axis if a beam bending magnet is not required. A simplified
block diagram of a medical linear accelerator is represented in fig. 1. The new frontier of
these machines is represented by multileaf collimator consisting of two of leaves (up to
120) which can be moved independently allowing the application of irregularly shaped
beams better adapted to the complex shape of the target volume. Moreover they permit
the application of special techniques like the intensity modulation (IMRT), dynamic
therapy and radiosurgery.
   New frontier in radiotherapy is nowadays represented by the use of hadrons. In fact
heavy particles (protons, light ions, neutrons) offer a unique opportunity for improving
the quality of radiation therapy. Their use has been pioneered over four decades at
Berkley where there was a very active collaboration among nuclear physicist, accelerator
physicist, physicians and biologist. This is well proven looking to the history of the
accelerators, especially of cyclotrons. E. Lawrence, the cyclotron father, started in thirties
a collaboration with physicians and biologist in the use of neutrons for cancer treatment.
The rationale base for the use of neutrons was not available at that time even if an
expected high incidence of late morbidity was shown. Only in sixties biologist showed
the role of the LET (Linear Energy Transfer) and the concept of radioresistance was
developed. In 1946 R. Wilson mentioned that the properties of mono—energetic charged
particles such as protons and Ions, i.e. the deposition of a large fraction of their kinetic
energy in a small volume at the end of their energy (BRAGG Peak and distal dose fall-
off), small lateral scattering, could lead to a new radiotherapic tool. The therapy with
heavy particles is based on two factors:
    -Balistic effect i.e. improved physical selectivity for charged particles, which means
the delivery of a homogeneous dose to the tumour volume while minimizing the dose to
surrounding healthy tissues.
    -Radiobiological effect i.e. the improved biological effectiveness (RBE) of hadrons
due to dense ionising tracks produced by these particles.
    In fig.2 you can see the comparison of depth-dose distribution for various types of
radiation used in radiotherapy. It is very clear and completely accepted that the
advantages of charged particles (protons, carbon ions) with respect to photons and
electrons are well summarized in the Bragg Peak and very reduced lateral scattering
permitting the better dose conformation to the tumour sparing surrounding healthy
tissues. RBE is assumed to be unitary for photons and electrons. It is well clear as
biological effectiveness can be significantly higher for hadrons especially for carbon ions.
According to that we can state that high-LET treatment is particularly useful for
radioresistent tumours, insensitive to conventional. These statements represent the
rationale that are convincing and forcing to develop hadrontherapy facility.
These facilities are typically based on the use of Cyclotrons and Synchrotrons. In the
PTCOG website [7]is reported a short list of these facilities. According to the already
gained clinical experience main advantages can be carried for tumours close to organ at
risk, like isolated brain metastases, pituitary adenomas, arteriovenous malformations,
base        of       skull      tumours,       meningiomas,        acoustic        neuromas
chordomas and chondrosarcomas, uveal melanomas, macular degeneration
head and neck tumours, chest and abdomen, medically inoperable non-small-cell lung
cancer, prostate, pediatric tumours (Brain, Orbital and ocular tumors, Sarcomas of the
base of skull and spine, Acoustic neuromas).
    Wide experience has been gained in the treatment of eye melanoma, considering the
reduced proton energy required, (around 62 MeV, corresponding to a beam range in
water of about 3 cm). In the following the experience gained at INFN-LNS will be
detailed reported.
    Beam produced by particle accelerators are not suitable for clinical applications if a
dedicated beam delivery system is not available. Any beam delivery system must
accomplish a three-dimensional scanning of the tumour requiring lateral beam deflection,
variable range and exposure time to achieve a uniform dose. Moreover position sensitive
monitors and fast beam switch-off in case of malfunction have to be available too. The
lateral beam deflection should be obtained either by passive scattering [8] or by active
methods using magnetic field deflecting the beam realizing a beam spot scanning . The
first method is implemented in fixed beam treatment line. At PSI a discrete spot scanning
system based on the use of a kicker magnet located within a gantry has been developed
and used for clinical application. The system is shown in fig.3. In order to reduce the
dose to surrounding healthy tissues we can take advantage by using different multiple
entrance beam port coming from different directions. A device performing this task is a
rotating gantry: the beam comes in along the axis, is guided away from the centre and
bent back towards the axis orthogonally. If the beam line ends at the axis so that the
patient is located opn the axis, the gantry is called isocentric. Isocentric gantry are
significantly different when applied at cyclotrons, characterized by a fixed extracted
beam energy or at synchrotrons able to change the extracted beam energy. In fig. 3 the
PSI Gantry is showed.

  5. HADRONTHERAPY FACILITIES

   Different commercial solutions are now available. A 235 MeV proton beam room-
temperature cyclotron has been studied and developed by IBA in Belgium. This cyclotron
with associated gantry has been installed at Massachusetts General Hospital in Boston
(USA) going in clinical operation in 2002.
   In 2001 PSI, Switzerland, announced officially to have chosen ACCEL Instruments
GmbH as the supplier of a 250 MeV superconducting cyclotron. The cyclotron will be
part of PSI´s proton therapy program PROSCAN. It includes the development of a
dedicated proton source and beamlines to supply up to 250 MeV protons to the existing
PSI Spot-Scanning-Gantry for deep-seated tumor treatment, a new industrialized Gantry
with advanced technical features and a horizontal beam for treatment of eye tumours.
ACCEL had proposed a very powerful proton accelerator based on a conceptual design
elaborated earlier by Prof. Henry Blosser and his team at the National Superconducting
Cyclotron Laboratory of Michigan State University. The 250 MeV cyclotron is designed
for highest extraction efficiency, low energy consumption, high reliability and most
modern operation features, e.g. spot scanning and beam intensity modulation. It uses
superconducting main coils allowing for moderate HV and RF power levels. The design
nevertheless provides full accessibility to the cyclotron parts relevant for operation and
maintenance. The cyclotron will be operable as a turn key system in mid 2004.
   In Italy an hadrontherapy facility is foreseen, the ‘Centro Nazionale di
Adroterapia’(CNA). It is a hospital based facility dedicated to advanced tumour
treatments with hadron beams and to advanced research (clinical, radiobiological and
technical) made possible by their availability. The main requirements, considered during
the CNA design, and the solutions adopted fully satisfy the following main criteria:
safety, reliability, maintainability and availability. These criteria have driven the
technological choices in so many respects that it is not possible to enumerate all of them
in this short introduction, but they will be the core arguments of the authorisation
documents that will be presented to obtain the permissions to run the centre and to treat
patients.
The CNA design (a preliminary view is shown in Fig. 4) is based on the following
assumptions:
•    the Centre will be devoted to the treatment of deep-seated tumours (up to a depth of
    27 cm of water equivalent) with light ion beams (mainly C6+, but also protons and
    possibly He2+, Li3+, Be4+, B5+ and O8+, but this last with a reduced range). All
    available light ions will be delivered in each treatment room with the exception of the
    room foreseen to be equipped, in a second stage, with a gantry for protons;
•    the full-size CNA will have 5 treatment rooms: 3 rooms with fixed beams and 2
     rooms with gantries. To reduce the initial investment it is proposed to first equip 3
     treatment rooms with 4 fixed beams, three horizontal and one vertical beams (CNA -
     Phase 1). At a later stage (CNA - Phase 2), two other rooms will be equipped with
     gantries: one gantry for protons and one gantry for light ions.
The eye melanoma treatment with proton beam represents the more significative clinical
experience. More than 7000 patients have been successfully treated in different facilities.
More significative experience has been gained in Europe at PSI, CCO and Nice, Orsay
and Berlin while in USA MGH and Loma Linda are the main centers [9].
      Also in Italy is now available a protontherapy center. In fact at the INFN Laboratori
Nazionali del Sud in Catania (Italy) the first Italian protontherapy facility, named
CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate) has been realized
in collaboration with the University of Catania.
It is based on the use of the 62 MeV proton beam delivered by the K=800
Superconducting Cylotron installed and working at LNS since 1995. The facility is
mainly devoted for the treatment of ocular diseases like uveal melanoma. A beam
treatment line in air has been realized together wth a dedicated positioning patient
system. The facility is in operation since the beginning of 2002 and 40 patients have been
successfully treated up to now. The CATANA proton beam line has been entirely
realized at LNS and its global view is shown in Fig.5. The proton beam exits in air
through 50 µm Kapton window placed at about 3 meters from isocenter. Before the
window, under vacuum, is placed the first scattering foil made by a 15 µm tantalum. The
first element of the beam in air is a second tantalum foil 25 µm thick provided with a
central brass stopper of 4 mm in diameter The double foils scattering system is optimized
to obtain a good homogeneity in terms of lateral dose distribution, minimizing the energy
loose. Range shifter and range modulator are placed downstream the scattering system
and mounted on two different boxes. Two diode lasers, placed orthogonally, provide a
system for the isocenter identification and for patient centering during the treatment. The
emission light of a third laser is spread out to obtain the simulation field.
     A key element of the treatment line is represented by the two transmission monitor
chambers and by the four sector chamber, implemented to have an on-line control of the
dose furnished to the patients and an information on beam symmetry respectively. The
last element before isocenter is a patient collimator located at 8 cm upstream of the
isocenter. Finally two, back and lateral, Philips Practics X-Rays tubes are mounted for the
verification of the treatment fields.
     Inside CATANA collaboration particular care is going to be devoted to the
development of dosimetric techniques for the determination of absorbed dose in clinical
proton beams and 2D and 3D dose distribution reconstruction. A parallel-plate calibrated
Markus ionization chamber has been chosen as reference detector for the absolute dose
measurement, while gaf chromic and radiographic films, TLD (ThermoLuminescent
Detectors), natural diamond and silicon detectors are the choices for the relative one.
Depth dose curves and transverse dose distributions, either for the full energy and
modulated proton beams, are acquired with a water-tank system provided of three fully
computer-controlled step motors. This system, entirely developed at Laboratori Nazionali
del Sud, is controlled by a software providing the acquisition and dosimetric analysis of
data. Figure 6 shows a depth dose distribution peak in water obtained with the water-tank
system and Markus chamber for an unmodulated 25 mm diameter beam at the energy of
62 AMeV.
    The Full Width at Half Maximum of the Bragg Peak is 2.76 mm while the 90-10 %
and 80-20% distal fall-off are 0.8 mm and 0.6 mm respectively. The entrance to peak
ratio is 4.72. We have realized, in collaboration with the Clatterbridge Center for
Oncology (UK), a set of wheel modulators to obtain a spread out therapeutic Bragg peak.
To do this various Bragg peaks, for different proton beam energies ranging from 62
AMeV to 10 AMeV, were acquired with the Markus chamber in the water phantom.
Proton beam energy lower than 62 AMeV are obtained inserting PMMA range shifters of
different thickness along the beam path. Finally Figure 7 shows the Spread Out Bragg
Peak obtained with the first prototype of the modulator wheel. Actually a first set of
modulator wheels (10, 12, 15, 20, 25 mm SOBP), developed for therapeutic purposes, are
available.
        Even if CATANA should not be the clinical answer for all the Italian patients
affected by this kind of disease it represents the first successfully Italian example of the
collaboration between Nuclear and Medical Physicist together with Medical Doctors in
fighting tumours with hadrons. CATANA is the first milestone in Italy trough the
extensive use of hadrontherapy in cancer treatment.
        Following this experience recently at LNS a new design of superconducting
cyclotron for medical applications has been proposed.. [12]. The design of the machine
model has been done to accelerate H21+, He2+,B5+, C6+up to 250 MeV/amu,
corresponding to a maximum average field at extraction radius of 3.8 tesla. The
accelerators will be the core of a new proposed hadrontherapy center that should be
realized in Catania in the next years, mainly devoted to the treatment of deep sited
tumours with proton beams and to clinical studies of some particular tumoural form with
carbon ions.


6. ACCELERATOR BASED FACILITY FOR RADIOISOTOPES PRODUCTION.

        Both Radioisotopes and enriched stable isotopes are essential to a wide variety of
applications in medicine, where they are used in the diagnosis and treatment of illness.
The radioisotopes produced for medical applications are tipically used in nuclear
medicine for diagnosis providing dynamic and functional information to study the organ
functions. The labelled biomolecules and radioisotopes involved should have as ideal
features the absence of beta particle emission, a half-life as short as possible and gamma
energy emission in a range between 100 and 300 keV. For a long period the production of
radioactive isotopes for medical applications was mainly based on neutron induced
nuclear reactions. This was essentially done in nuclear reactors but their availability is
slowly decreasing so that the accelerators based production facility are growing up. It is
well known and proven that Short life radioisotopes (Fluorine-18, carbon-11, Nitrogen-13
and oxygen-15) are tipically accelerator produced radionuclides. Also others
Radionuclides (gallium-67, Indium-111, iodine-123, thallium-201) are produced by
means of 30 MeV cyclotrons for loco-regional distribution. According to those a wide
market of turn-key accelerators is nowadays available. The main choice in this field is
represented by cyclotrons. Infact looking to the time structure of the extracted beam,
cyclotrons represent the golden standard with respect to linacs. It si possible to state that
the power deposition in a production target is significantly better using a cyclotron which
it is characterized by a beam time structure that can be assumed as a “ practically
continuous beam”. Linacs are characterized by a low repetition rate so that the
instantaneous power deposition in the target so high that force to implement very
complex solution expecially in the material choice for thermal dissipation.
        Even if it is possible to state that with a 30 MeV should be possible to produce
many radioisotopes of interest for medical application, it is growing the demand of
production of radionuclides requiring a primary proton energy at energy higher then 30
MeV like Magnesium-28, iron-52, germanium-68, strontium-82, xenon-122/127,
astanium-201. These demands are also forcing to try to use already existing high intensity
nuclear facilities that should be partially involved in this task.
        Modern isotope production facilities consists of a compact H- cyclotron in the
nergy range between 10 and 30 MeV with extracted current up to 400 microA and highly
sophisticated target technology and chemistry. Target can be made solid, gas or liquid. In
any case they have to be designed in order to dissipate up to 10 kW. A temperature rise of
150 °C is well accepted. The choice of material is dependent on the particular nuclide
process. Although a general rule does not exist, there are some aspects of target body like
activation, contamination, corrosion and cooling, have to be kindly considered. Target
can be either internal and external, placed at the end of dedicated beam transport lines. In
tab. 1 the most common cyclotron produced radioisotopes for medical diagnostics are
reported.
        Different commercial solutions are available. IBA, General Electric, CTI, EBCO
and SUMITOMO are the main cyclotron producers. They also offer dedicated
radiochemistry modules for the production of the labelled molecula to be used. A typical
production plant is reported in fig. 8

7. CONCLUSIONS

The role of particle accelerators is rising for medical applications. The synergy between
medicine (radiotherapy, radiology, nuclear medicine, oncology) and physics (nuclear and
accelerator physics) is growing even more and will represent the future challenge to get a
better quality of life in the third millennium. The number of potential patients for
hadrontherapy have been determined in many studies with different results [9,10,11]. It is
possible to state that the percentage of patients getting advantage with respect to
conventional radiotherapy is of the order of 30%. Moreover the exploitation of
accelerator based facility for the radioisotope production should significantly rise the
medical imaging performance permitting an early stage diagnosis of many important
diseases, first of all tumours. In conclusion we want to stress again as many advantage
can be carried out using particle accelerators for medical applications.
REFERENCE

[1]U. Amaldi, Nuclear Physics A654 (1999)375C-399C
[2]A.J.M. Vrmoken and F.A.T.M. Schermer (eds), Amsterdam, Oxford, Washnghton DC,
Tokyo: IOS press, (1994)
[3]S. Webb, IMRT, IOP 2001
[4]S. Webb, The physics of conformal radiotherapy, IOP 2001
[5]C. Van de Wiele, Int. J. Radiation Oncology Biol. Phys, Vol. 55 No1, pp5-15, 2003
[6]CAS Cern Accelerator school: Cyclotrons, linacs and their applications, CERN 96-02
[7] www.ptcog.web.psi.ch
[8]B. Gottshalck et al., Harvard Cyclotron Laboratory, report 3/29/89 (1989)
[9]Advances in Hadrontherapy, U. Amaldi, B. Larsson and Y. Lemoigne eds, Excerpta
Medica, 1996
[10]G. Gademan, ref [10], p.59
[11]R. Orecchia et al. Eur. J. Cancer (1998), p.459
[12] L. Calabretta, XXXV PTCOG Abstract, 2002
                   Tab. 1. List of some radioisotope tipically used for medical applications



             Nuclear             Proton          Decay            T1/2
Radioisot.   Reaction            Energy         Product                     Emission Application
                                 (MeV)
   15        15                                    14
        O       N(p,n)
                15
                                 10→0                   N       2.03m           β+             PET
   13         13 O                                  13            in
        N       C(p,n)           10→0                    C       9.96           β+             PET
                13
   11         11 N                                  11           min
        C       B(p,n)
                11
                                 10→0                    B       20.38          β+             PET
   18        18    C                               18             min
        F       O(p,n)           16→3                   O        109.8          β+             PET
  111        112
                  18
                     F
                 Cd(p,2n)1                        111             min
        In          11
                         In
                                    22                  Cd        68 h         EC          Radioim
             124                                                                            mun
   123
         I     Xe(p,2n)1            30            123
                                                        Te      13.2 h         EC           Brain
                23
                   Cs→
             123
                 Xe→123I                                                                    Spect
  67         68                                    67
       Cu         Zn(p,2p)
                   67
                                    40                  Zn      61.9 h          β-         Radioim
                      Cu
  122        127                                    122
                                                                                            mun
        Xe     I(p,6                70                    I     20.1 h         EC         Father positron
               122                                                                          emitter 122I
             n) Xe
  68         nat                                   68
       Ge     Ge(p,p                70                  Ga       271 d         EC          PET and
             xn) 68Ge                                                                      tumoral
                                                                                            marker
Fig




      Fig. 1 Schematic view of a conventional LINAC (Courtesy by VARIAN)
Fig. 2 Photons, electrons and protons Depth Dose




               Fig . 3 PSI Gantry
Fig. 4 – CNA: preliminary design of the CNA – Phase 1. The
synchrotron and the lines that serve three treatment rooms are
evidenced.




Figure 5. View of the CATANA beam line: 1.Treatment chair for patient
immobilization, 2. Final collimator, 3.Positioning laser, 4. Light field simulator; 5. A
Monitor chamber; 6. Intermediate collimator, 7-8.Boxes for the location of
modulator wheel and range shifter, 9.Proton beam output window.
                                 5
                        4.5
                                 4
                        3.5
 Ionization [a.u.]



                                 3
                        2.5
                                 2
                        1.5
                                 1
                        0.5
                                 0
                                            0                     5       10           15        20        25    30   35
                                                                                    Depth in water [mm]

Figure 6. Bragg peak of 62 AMeV proton Beam acquired with a water-
 tank system and a Markus chamber ionization chamber at CATANA
                              facility

                                                        110
                     Dose normalized at maximum value




                                                        100
                                                        90
                                                        80
                                                        70
                                   [a.u.]




                                                        60
                                                        50
                                                        40
                                                        30
                                                        20
                                                        10
                                                         0
                                                              0       5        10           15        20    25   30   35

                                                                                    Depth in water [mm]

  Figure 7 Spread Out Bragg Peak obtained with a modulator wheel;
                       Data acquired in water
Fig. 8 A typical PET center (courtesy by IBA)